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PDCD5 binds OTUD5. 23 / 28
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"Therefore, dysregulation of p53-interacting deubiquitinating enzymes may lead to aberrant regulation of genotoxic responses in cancer cells.To understand how the tumor suppressor PDCD5 is regulated du[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, knocking-down of OTUD5 markedly diminished the association of PDCD5 with p53, indicating that OTUD5 binds to PDCD5 and mediates PDCD5-p53 network during genotoxic stress responses ( Fig. 1B )[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Thus, we next explored the possibility that OTUD5 initially binds to and stabilizes PDCD5 and subsequently stabilizes p53 in response to genotoxic stress."
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"However, upon prolonged genotoxic stress, the interaction between OTUD5 and PDCD5 was reduced, while the association between OTUD5 and p53 gradually increased, leading to p53 induction ( Fig. 4A )."
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"We corroborated these findings by a reconstitution experiment where a point mutant defective for interaction with OTUD5 (PDCD5 E94D ) showed that OTUD5 interaction with PDCD5 is a prerequisite for p53[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Park et al ( xref ) identified the programmed cell death 5-OTUD5 network as a central hub for regulating p53-mediated apoptosis."
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"Under genotoxic stress, OTUD5 binds to PDCD5 and increases PDCD5 stability by mediating the deubiquitination of PDCD5 [ xref ]."
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"Park et al. xref further revealed that deubiquitinase OTUD5 directly binds to PDCD5 and promotes its accumulation by mediating PDCD5 deubiquitination at Lys‐97/98 upon genotoxic stress‐induced apoptosis."
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"To understand how the tumor suppressor PDCD5 is regulated during apoptosis, we employed yeast two-hybrid assays to identify interacting partners of PDCD5 and found that OTUD5 bound to PDCD5 in respons[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Park and colleagues [17] found that OTUD5 binds to PDCD5 in response to etoposide treatment via its ubiquitin interacting motif (UIM)."
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"However, knocking-down of OTUD5 markedly diminished the association of PDCD5 with p53, indicating that OTUD5 binds to PDCD5 and mediates PDCD5-p53 network during genotoxic stress responses ( Fig. 1B )[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Under genotoxic stress, OTUD5 binds to PDCD5 and increases PDCD5 stability by mediating the deubiquitination of PDCD5 [22]."
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"90–125) of PDCD5 interacted with OTUD5 (Appendix: Supplementary Fig. S1 A)."
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"Moreover, OTUD5 interacts with PDCD5 in response to etoposides, which is a prerequisite for the stabilization and activation of p53 xref , xref ."
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"Thus, we next explored the possibility that OTUD5 initially binds to and stabilizes PDCD5 and subsequently stabilizes p53 in response to genotoxic stress."
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"Park and colleagues [17] found that OTUD5 binds to PDCD5 in response to etoposide treatment via its ubiquitin interacting motif (UIM)."
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"At the early phase of ET treatment (1 h), PDCD5 levels were increased and OTUD5 strongly interacted with PDCD5 rather than with p53 ( Fig. 4A )."
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"However, upon prolonged genotoxic stress, the interaction between OTUD5 and PDCD5 was reduced, while the association between OTUD5 and p53 gradually increased, leading to p53 induction ( Fig. 4A )."
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"Mapping analysis demonstrated that the C-terminal domain (Q90–Y125) of PDCD5 interacts with OTUD5, and the N-terminal domain (M1–Q30) of PDCD5 interacts with TP53."
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"When OTUD5 was depleted, PDCD5 failed to activate TP53, demonstrating an essential role for the PDCD5–OTUD5 network in TP53-mediated apoptosis in response to genotoxic stress."
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"Park et al. 35 further revealed that deubiquitinase OTUD5 directly binds to PDCD5 and promotes its accumulation by mediating PDCD5 deubiquitination at Lys‐97/98 upon genotoxic stress‐induced apoptosis."
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"We corroborated these findings by a reconstitution experiment where a point mutant defective for interaction with OTUD5 (PDCD5 E94D ) showed that OTUD5 interaction with PDCD5 is a prerequisite for p53[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Together, our findings reveal a previously undiscovered PDCD5-OTUD5 network that acts as a central hub in the regulation of p53-mediated apoptosis."
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